2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs.

Endpoint summary

Description of key information

2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs. is neither a skin nor an eye irritant.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Age :10 to 12 weeks
Sex :Female
Body weight range : 1.80kg±200g
No. of animals :Three
Acclimatization : The healthy rabbits selected for study was acclimatized to standard laboratory condition for one week in experimental room under Veterinary examination.
Environmental conditions : Air conditioned rooms with 10-15 air changes per hour, temperature between 22-250C, relative humidity 40-60% and illumination cycle set to 12 hours artificial fluorescent light and 12 hours dark.

Type of coverage:

open

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

0.5 ml

Duration of treatment / exposure:

4 hrs

Observation period:

60 min., 24, 48 and 72 hours after application.

Number of animals:

No. of animals : Three

Details on study design:

Initial test (using one animal)
In the initial test one healthy rabbit of body weight 2.18 kg selected for study after acclimatization. The test compound in the amount of 0.5 ml (as the compound was in the liquid form) was applied uniformly at the different sites on the shaven back skin of animal. The hairs of back sides were removed (approximately 6 cm2) one day earlier before the treatment.
The test substance 2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs in the amount of 0.5 ml was applied to a small area (approximately 6 cm2) of skin and covered with a gauze patch, which was held in place with non-irritating tape. The first patch was applied on the shaven back skin of rabbit and removed after three minutes. No serious reaction was observed at the site of application. The second patch was applied on the different shaven back side and removed after one hour. There were no signs of skin reaction observed at this site of application. Finally, a third patch was applied at a different site and was removed after four hour. Slight redness was observed at the site of application of the test compound after 4 hours of patch removal. Finally, the animal was observed for 14 days, for any irritation and corrosion.

Confirmatory test (with addition animals):
Because of there was no corrosive effect was observed in the initial test, a confirmatory test was done in order to confirm the irritant or negative response of the test substance by using two additional animals.
In the confirmatory test the test compound in the amount of 0.5 ml was applied on the shaven back skin (approximately 6 cm2) of two animals, each with one patch, for an exposure period of four hours.
After four hours the patch was removed and the skin reactions were graded according to Draize’s method. The test compound 2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs when applied dermally on New Zealand White rabbit in the amount of 0.5 ml produced slight erythema upto 24 hours. Furthermore, no clinical signs were observed during the entire observation period.
The dermal irritation index of New Zealand white rabbits is calculated as 0.42 and test compound can be classified under slightly irritant at the tested dose level.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Score:

0.42

Reversibility:

no data

Irritant / corrosive response data:

Skin reaction
The test compound 2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs when applied in the amount of 0.5 ml on the shaven back skin (approximately 6 cm2) of New Zealand white rabbit produced slight redness after four hours of patch removal upto 24 hours. No other skin reactions were recorded after 24 hours

Other effects:

The test compound 2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs applied on the shaven back skin of rabbit in the amount of 0.5 ml did not produce pain and any clinical signs of toxicity throughout the examination period of 14 days.

INDIVIDUAL ANIMAL DERMAL IRRITATION SCORES

 

Rabbit No.	Sex	INTACT SKIN
		3 Min.		4 Hours		24 Hours		48 Hours		72 Hours		14 days
		Erythema	Oedema	Erythema	Oedema	Erythema	Oedema	Erythema	Oedema	Erythema	Oedema	Erythema	Oedema
01	F	0	0	1	0	1	0	0	0	0	0	0	0
02	F	-	-	1	0	0	0	0	0	0	0	0	0
03	F	-	-	1	0	1	0	0	0	0	0	0	0
Total		0	0	3	0	2	0	0	0	0	0	0	0
Mean		0	0	1	0	0.66	0	0	0	0	0	0	0
Grand Total		1.67

 

Dermal Irritation Index: 1.67/4 = 0.42

Interpretation of results:

slightly irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

From the above result it can be concluded that the test compound 2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs is slightly irritant to skin at the tested dose level of 0.5 ml in New Zealand white rabbits under test condition.

Executive summary:

From the above result it can be concluded that the test compound 2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs is slightly irritant to skin at the tested dose level of 0.5 ml in New Zealand white rabbits under test condition.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Age : 10 to 12 weeks
Sex : Female
Body weight range : 1.80kg ±200g
No. of animals : Three
Acclimatization : The rabbit was acclimatized to standard laboratory condition for 24 hours in experimental room before study
Environmental conditions : Air conditioned room with 10-15 air changes per hour, temperature between 22-250C, relative humidity 40-60% and illumination cycle set to 12 hours artificial fluorescent light and 12 hours dark.

Amount / concentration applied:

A dose of 0.1gm of test substance was applied into the one eye of the rabbits. The other eye, which remains untreated, serves as a control.

Duration of treatment / exposure:

24 hrs

Observation period (in vivo):

The eyes were examined at 1, 24, 48 and 72 hours after test substance application. The grades of ocular reaction (conjunctiva, cornea and iris) were recorded at each observation. To determine the reversibility of the effect the animal was observed normally for 21 days. Any other lesions in the eye viz pannus, staining were observed and scored accordingly. Examination of reactions was facilitated by use of biomicroscope and hand slit lamp. After recording the observations at 24 hours, the eyes were further examined with the aid of fluorescein. Individual animal weight before and during the study was also observed

Number of animals or in vitro replicates:

No. of animals : Three

Details on study design:

TEST PROCEDURE:
The test compound 2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs in the amount of 0.1 ml applied in the conjunctival sac of one eye of each animal after gentle pulling the lower eye lid away from the eye ball. The eye lids were then gently held together for about one second to prevent the loss of the material. The other eyes which remains untreated, served as control.
Irritation:
The eyes of the test animal did not washed for at least 24 hours following instillation of the test compound. At 24 hours a washout may be used if considered appropriate.

Irritation parameter:

other: MMAS(Modified Maximum Average Draizes Test Score)

Basis:

mean

Score:

8.33

Reversibility:

not specified

Remarks on result:

other: not irritating

Irritant / corrosive response data:

The test compound 2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs when applied to the eye of New Zealand white rabbit at the dose level of 0.1 gm produce slight redness and mild eye discharge after four hours of application of test compound. However, any lesions such as pannus, staining were not recorded throughout the observation period of 72 hours.

      GRADING OF OCULAR LESIONS

 

S.NO/ SEX		OBSERVATION	Score				Total	Total Score
1/F			1 hour	24hours	48 hours	72 hours
	Cornea	A.       Opacity-Degree of Density	0	0	0	0	0	0×0×5=0
		B.       Area of Cornea Involved	0	0	0	0	0
	Iris	A.       Values	0	0	0	0	0	0
	Conjunctivae	A.       Redness	1	0	0	0	1	1+0+1×5=10
		B.       Chemosis	0	0	0	0	0
		C.       Discharge	0	1	0	0	0
2/F	Cornea	A.       Opacity-Degree of Density	0	0	0	0	0	0×0×5=0
		B.       Area of Cornea Involved	0	0	0	0	0
	Iris	A.       Values	0	0	0	0	0	0
	Conjunctivae	A.       Redness	1	0	0	0	1	1+0+0×5=5
		B.       Chemosis	0	0	0	0	0
		C.       Discharge	0	0	0	0	0
3/F	Cornea	A.       Opacity-Degree of Density	0	0	0	0	0	0×0×5=0
		B.       Area of Cornea Involved	0	0	0	0	0
	Iris	A.       Values	0	0	0	0	0	0
	Conjunctivae	A.       Redness	1	0	0	0	1	1+0+1×5=10
		B.       Chemosis	0	0	0	0	0
		C.       Discharge	0	1	0	0	0
Grand total								25
Mean								8.33
Eye Irritation Scoring index								2.08

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The Modified maximum average score (MMAS) of 2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs was found to be 8.33.
Based on above results, it can be concluded that the test compound 2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs is practically non irritant when applied in the amount of 0.1 gm in the conjunctival sac of the New Zealand White rabbits.

Executive summary:

The Modified maximum average score (MMAS) of 2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs was found to be 8.33.

Based on above results, it can be concluded that the test compound 2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs is practically non irritant when applied in the amount of 0.1 gm in the conjunctival sac of the New Zealand White rabbits.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Skin irritation-

Based on studies of target substance 2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs. and readacross substances reviewed for skin irritation from reliable sources having Klimisch rating 1 and 4 considering the weight of evidence approach.

 The summary of the results are presented below

Sr. No	End point	effect	Species	Remark
1.	primary dermal irritation index (PDII)	slightly irritating	Rabbit	IIRT Results
2.	overall irritation score	Not irritating	Rabbit	RA 2783-94-0(Study report)

 

Based on the results summarized above it is assessed that the test substance 2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs. Is slightly irritating. However the data is insufficient to classify the substance as an skin irritant.Thus considering the target and readacross data and as per the CLP criteria the substance 2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs. Is not classified as an skin irritant.

Eye irritation-

Based on studies of target substance 2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs. and readacross substances reviewed for eye irritation from reliable sources having Klimisch rating 1 and 4 considering the weight of evidence approach.

 The summary of the results are presented below

Sr. No	End point	effect	Species	Remark
1.	primary dermal irritation index (PDII)	Not irritating	Rabbit	IIRT Results
2.	overall irritation score	Not irritating	Rabbit	RA 2783-94-0(Study report)

Based on the results summarized above and considering and CLP criteria it is assessed that the test substance 2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs. Is not an eye irritant.

Justification for selection of skin irritation / corrosion endpoint:

From the above result  it can be concluded that the test compound 2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs is slightly irritant to skin at the tested dose level of 0.5 ml in New Zealand white rabbits under test condition.

Justification for selection of eye irritation endpoint:

The Modified maximum average score (MMAS) of 2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs was found to be 8.33.

Based on above results, it can be concluded that the test compound 2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs  is practically non irritant when applied in the amount of 0.1 gm in the conjunctival sac of the  New Zealand White rabbits.

Justification for classification or non-classification

The test substance 2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs is neither a skin nor an eye irritant as per the CLP regulation.